Propensity Score-Matching Analysis Comparing Robotic Versus Laparoscopic Limited Liver Resections of the Posterosuperior Segments: An International Multicenter Study.

OBJECTIVE: The purpose of this study was to compare the outcomes of robotic limited liver resections (RLLR) versus laparoscopic limited liver resections (LLLR) of the posterosuperior segments. BACKGROUND: Both laparoscopic and robotic liver resections have been used for tumors in the posterosuperior liver segments. However, the comparative performance and safety of both approaches have not been well examined in the existing literature. METHODS: This is a post hoc analysis of a multicenter database of 5446 patients who underwent RLLR or LLLR of the posterosuperior segments (I, IVa, VII, and VIII) at 60 international centers between 2008 and 2021. Data on baseline demographics, center experience and volume, tumor features, and perioperative characteristics were collected and analyzed. Propensity score-matching (PSM) analysis (in both 1:1 and 1:2 ratios) was performed to minimize selection bias. RESULTS: A total of 3510 cases met the study criteria, of whom 3049 underwent LLLR (87%), and 461 underwent RLLR (13%). After PSM (1:1: and 1:2), RLLR was associated with a lower open conversion rate [10 of 449 (2.2%) vs 54 of 898 (6.0%); P =0.002], less blood loss [100 mL [IQR: 50-200) days vs 150 mL (IQR: 50-350); P <0.001] and a shorter operative time (188 min (IQR: 140-270) vs 222 min (IQR: 158-300); P <0.001]. These improved perioperative outcomes associated with RLLR were similarly seen in a subset analysis of patients with cirrhosis-lower open conversion rate [1 of 136 (0.7%) vs 17 of 272 (6.2%); P =0.009], less blood loss [100 mL (IQR: 48-200) vs 160 mL (IQR: 50-400); P <0.001], and shorter operative time [190 min (IQR: 141-258) vs 230 min (IQR: 160-312); P =0.003]. Postoperative outcomes in terms of readmission, morbidity and mortality were similar between RLLR and LLLR in both the overall PSM cohort and cirrhosis patient subset. CONCLUSIONS: RLLR for the posterosuperior segments was associated with superior perioperative outcomes in terms of decreased operative time, blood loss, and open conversion rate when compared with LLLR.

Defining Global Benchmarks for Laparoscopic Right Posterior Sectionectomy/H67: An International Multicenter Study.

OBJECTIVE: We aimed to establish global benchmark outcomes indicators for L-RPS/H67. BACKGROUND: Minimally invasive liver resections has seen an increase in uptake in recent years. Over time, challenging procedures as laparoscopic right posterior sectionectomies (L-RPS)/H67 are also increasingly adopted. METHODS: This is a post hoc analysis of a multicenter database of 854 patients undergoing minimally invasive RPS (MI-RPS) in 57 international centers in 4 continents between 2015 and 2021. There were 651 pure L-RPS and 160 robotic RPS (R-RPS). Sixteen outcome indicators of low-risk L-RPS cases were selected to establish benchmark cutoffs. The 75th percentile of individual center medians for a given outcome indicator was set as the benchmark cutoff. RESULTS: There were 573 L-RPS/H67 performed in 43 expert centers, of which 254 L-RPS/H67 (44.3%) cases qualified as low risk benchmark cases. The benchmark outcomes established for operation time, open conversion rate, blood loss ≥500 mL, blood transfusion rate, postoperative morbidity, major morbidity, 90-day mortality and textbook outcome after L-RPS were 350.8 minutes, 12.5%, 53.8%, 22.9%, 23.8%, 2.8%, 0% and 4% respectively. CONCLUSIONS: The present study established the first global benchmark values for L-RPS/H6/7. The benchmark provided an up-to-date reference of best achievable outcomes for surgical auditing and benchmarking.

Robotic Versus Laparoscopic Liver Resection in Various Settings: An International Multicenter Propensity Score Matched Study of 10.075 Patients.

OBJECTIVE: To compare the perioperative outcomes of robotic liver surgery (RLS) and laparoscopic liver surgery (LLS) in various settings. BACKGROUND: Clear advantages of RLS over LLS have rarely been demonstrated, and the associated costs of robotic surgery are generally higher than those of laparoscopic surgery. Therefore, the exact role of the robotic approach in minimally invasive liver surgery remains to be defined. METHODS: In this international retrospective cohort study, the outcomes of patients who underwent RLS and LLS for all indications between 2009 and 2021 in 34 hepatobiliary referral centers were compared. Subgroup analyses were performed to compare both approaches across several types of procedures: (1) minor resections in the anterolateral (2, 3, 4b, 5, and 6) or (2) posterosuperior segments (1, 4a, 7, 8), and (3) major resections (≥3 contiguous segments). Propensity score matching was used to mitigate the influence of selection bias. The primary outcome was textbook outcome in liver surgery (TOLS), previously defined as the absence of intraoperative incidents ≥grade 2, postoperative bile leak ≥grade B, severe morbidity, readmission, and 90-day or in-hospital mortality with the presence of an R0 resection margin in case of malignancy. The absence of a prolonged length of stay was added to define TOLS+. RESULTS: Among the 10.075 included patients, 1.507 underwent RLS and 8.568 LLS. After propensity score matching, both groups constituted 1.505 patients. RLS was associated with higher rates of TOLS (78.3% vs 71.8%, P < 0.001) and TOLS+ (55% vs 50.4%, P = 0.026), less Pringle usage (39.1% vs 47.1%, P < 0.001), blood loss (100 vs 200 milliliters, P < 0.001), transfusions (4.9% vs 7.9%, P = 0.003), conversions (2.7% vs 8.8%, P < 0.001), overall morbidity (19.3% vs 25.7%, P < 0.001), and microscopically irradical resection margins (10.1% vs. 13.8%, P = 0.015), and shorter operative times (190 vs 210 minutes, P = 0.015). In the subgroups, RLS tended to have higher TOLS rates, compared with LLS, for minor resections in the posterosuperior segments (n = 431 per group, 75.9% vs 71.2%, P = 0.184) and major resections (n = 321 per group, 72.9% vs 67.5%, P = 0.086), although these differences did not reach statistical significance. CONCLUSIONS: While both produce excellent outcomes, RLS might facilitate slightly higher TOLS rates than LLS.

Radiomics of Intrahepatic Cholangiocarcinoma and Peritumoral Tissue Predicts Postoperative Survival: Development of a CT-Based Clinical-Radiomic Model.

BACKGROUND: For many tumors, radiomics provided a relevant prognostic contribution. This study tested whether the computed tomography (CT)-based textural features of intrahepatic cholangiocarcinoma (ICC) and peritumoral tissue improve the prediction of survival after resection compared with the standard clinical indices. METHODS: All consecutive patients affected by ICC who underwent hepatectomy at six high-volume centers (2009-2019) were considered for the study. The arterial and portal phases of CT performed fewer than 60 days before surgery were analyzed. A manual segmentation of the tumor was performed (Tumor-VOI). A 5-mm volume expansion then was applied to identify the peritumoral tissue (Margin-VOI). RESULTS: The study enrolled 215 patients. After a median follow-up period of 28 months, the overall survival (OS) rate was 57.0%, and the progression-free survival (PFS) rate was 34.9% at 3 years. The clinical predictive model of OS had a C-index of 0.681. The addition of radiomic features led to a progressive improvement of performances (C-index of 0.71, including the portal Tumor-VOI, C-index of 0.752 including the portal Tumor- and Margin-VOI, C-index of 0.764, including all VOIs of the portal and arterial phases). The latter model combined clinical variables (CA19-9 and tumor pattern), tumor indices (density, homogeneity), margin data (kurtosis, compacity, shape), and GLRLM indices. The model had performance equivalent to that of the postoperative clinical model including the pathology data (C-index of 0.765). The same results were observed for PFS. CONCLUSIONS: The radiomics of ICC and peritumoral tissue extracted from preoperative CT improves the prediction of survival. Both the portal and arterial phases should be considered. Radiomic and clinical data are complementary and achieve a preoperative estimation of prognosis equivalent to that achieved in the postoperative setting.

Impact of Liver Cirrhosis, Severity of Cirrhosis, and Portal Hypertension on the Difficulty and Outcomes of Laparoscopic and Robotic Major Liver Resections for Primary Liver Malignancies.

BACKGROUND: Minimally invasive liver resections (MILR) offer potential benefits such as reduced blood loss and morbidity compared with open liver resections. Several studies have suggested that the impact of cirrhosis differs according to the extent and complexity of resection. Our aim was to investigate the impact of cirrhosis on the difficulty and outcomes of MILR, focusing on major hepatectomies. METHODS: A total of 2534 patients undergoing minimally invasive major hepatectomies (MIMH) for primary malignancies across 58 centers worldwide were retrospectively reviewed. Propensity score (PSM) and coarsened exact matching (CEM) were used to compare patients with and without cirrhosis. RESULTS: A total of 1353 patients (53%) had no cirrhosis, 1065 (42%) had Child-Pugh A and 116 (4%) had Child-Pugh B cirrhosis. Matched comparison between non-cirrhotics vs Child-Pugh A cirrhosis demonstrated comparable blood loss. However, after PSM, postoperative morbidity and length of hospitalization was significantly greater in Child-Pugh A cirrhosis, but these were not statistically significant with CEM. Comparison between Child-Pugh A and Child-Pugh B cirrhosis demonstrated the latter had significantly higher transfusion rates and longer hospitalization after PSM, but not after CEM. Comparison of patients with cirrhosis of all grades with and without portal hypertension demonstrated no significant difference in all major perioperative outcomes after PSM and CEM. CONCLUSIONS: The presence and severity of cirrhosis affected the difficulty and impacted the outcomes of MIMH, resulting in higher blood transfusion rates, increased postoperative morbidity, and longer hospitalization in patients with more advanced cirrhosis. As such, future difficulty scoring systems for MIMH should incorporate liver cirrhosis and its severity as variables.

Feasibility and operative outcomes of surgery in the liver area in advanced ovarian cancer.

OBJECTIVE: The study aimed to characterize intra-and postoperative complications according to a standardized anatomo-surgical classification for ovarian cancer metastases in the liver area. METHODS: Data from all patients with advanced ovarian cancer undergoing primary or secondary surgery with perihepatic liver involvement (May-2016 to May-2022), were retrospectively retrieved and classified according to a standardized anatomo-surgical classification, and clustered into four Classes: Class I "Peritoneal", Class II "Hepatoceliac-lymph-nodes", Class III "Parenchymal" and Class IV Mixed (≥ 2 classes). RESULTS: Data from 615 patients were collected. Intraoperative complications were observed in 15%, and severe postoperative complications in 17.6% of cases. While surgical complexity scores were similar, Class IV had longer operative times, higher blood loss, and a 30.4% intraoperative transfusion rate. Class II showed a higher prevalence of vascular injuries (8%). Classes II and IV were significantly associated with severe postoperative complications. Specific complications varied among classes, such as perihepatic collection and intrahepatic hematoma/abscess in Class III (p = 0.003, p < 0.001, respectively), and pleuric effusion, sepsis, anemia, and "other complications" in Class IV (p = 0.002, p = 0.004, p = 0.03, p = 0.03, respectively). Multivariable analysis identified Class II and IV (Class II: OR 4.991, p = 0.045; Class IV: OR 5.331, p = 0.030), Surgical Complexity Score group 3 (OR:3.922, p = 0.003), and the presence of residual tumor (OR:1.748, p = 0.048) as independent risk factors for severe postoperative complications. CONCLUSIONS: Liver procedures during advanced ovarian cancer surgery are feasible with acceptable complication rates According to the anatomo-surgical classification, metastatic patterns are related to both different surgical outcomes and postoperative complication profiles.

Hug sign in intraprocedural cone-beam-CT to predict short-term response to combined treatment of hepatocellular carcinoma.

OBJECTIVES: Combined treatment of ablation and chemoembolization for hepatocellular carcinoma represents a promising therapy to increase treatment efficacy and improve patient survival. The "hug sign" is a recently introduced radiological sign consisting in deposition of beads/contrast agent during transarterial chemoembolization in the hyperemic area surrounding the post-ablation volume, seen during intraprocedural unenhanced cone-beam CT, that may indicate intraprocedural success. Aim of our retrospective study was to analyze the usefulness of the "hug sign" at the intraprocedural unenhanced cone-beam CT as an early predictor of response to combined treatment, based on the hug sign angle. MATERIALS AND METHODS: Between January 2017 and September 2021 all patients with hepatocellular carcinoma which underwent a combined treatment of thermal ablation followed by chemoembolization were enrolled. All treated patients underwent immediate post-procedural unenhanced cone-beam CT to evaluate the deposition of contrast agent, lipiodol or radiopaque beads and to assess the percentage of coverage of the ablated area with the contrast agent (hug sign angle). Patients with missing pre-procedural, intra-procedural and/or post-procedural data/imaging, or with poor-quality post-procedural cone-beam CT images were excluded. RESULTS: 128 patients (mean age, 69.3 years ± 1.1 [standard deviation]; 87 men) were evaluated. Our study evidenced that 84.4% (81/85) of patients with a hug sign angle of 360° had no residual tumor at the first 1-/3-months follow-up examination. A hug sign angle of 360° also showed to be an independent protective factor against residual tumor at multivariate analysis. CONCLUSION: Unenhanced cone-beam CT performed at the end of a combined treatment with ablation plus chemoembolization can effectively predict an early treatment response on radiological images, when a hug sign angle of 360° was detected.

Trends in the characteristics and perioperative outcomes of patients undergoing laparoscopic and open resections for benign liver lesions: An international multicenter retrospective cohort study of 845 patients.

BACKGROUND: Solid benign liver lesions (BLL) are increasingly discovered, but clear indications for surgical treatment are often lacking. Concomitantly, laparoscopic liver surgery is increasingly performed. The aim of this study was to assess if the availability of laparoscopic surgery has had an impact on the characteristics and perioperative outcomes of patients with BLL. METHODS: This is a retrospective international multicenter cohort study, including patients undergoing a laparoscopic or open liver resection for BLL from 19 centers in eight countries. Patients were divided according to the time period in which they underwent surgery (2008-2013, 2014-2016, and 2017-2019). Unadjusted and risk-adjusted (using logistic regression) time-trend analyses were performed. The primary outcome was textbook outcome (TOLS), defined as the absence of intraoperative incidents ≥ grade 2, bile leak ≥ grade B, severe complications, readmission and 90-day or in-hospital mortality, with the absence of a prolonged length of stay added to define TOLS+. RESULTS: In the complete dataset comprised of patients that underwent liver surgery for all indications, the proportion of patients undergoing liver surgery for benign disease remained stable (12.6% in the first time period, 11.9% in the second time period and 12.1% in the last time period, p = 0.454). Overall, 845 patients undergoing a liver resection for BLL in the first (n = 374), second (n = 258) or third time period (n = 213) were included. The rates of ASA-scores≥3 (9.9%-16%,p < 0.001), laparoscopic surgery (57.8%-77%,p < 0.001), and Pringle maneuver use (33.2%-47.2%,p = 0.001) increased, whereas the length of stay decreased (5 to 4 days,p < 0.001). There were no significant changes in the TOLS rate (86.6%-81.3%,p = 0.151), while the TOLS + rate increased from 41.7% to 58.7% (p < 0.001). The latter result was confirmed in the risk-adjusted analyses (aOR 1.849,p = 0.004). CONCLUSION: The surgical treatment of BLL has evolved with an increased implementation of the laparoscopic approach and a decreased length of stay. This evolution was paralleled by stable TOLS rates above 80% and an increase in the TOLS + rate.

Survival benefit of adequate lymphadenectomy in patients undergoing liver resection for clinically node-negative intrahepatic cholangiocarcinoma.

BACKGROUND & AIMS: Lymph-nodal status is an important predictor of survival in intrahepatic cholangiocarcinoma (iCCA), but the need to perform lymphadenectomy in patients with clinically node-negative (cN0) iCCA is still under debate. The aim of this study was to determine whether adequate lymphadenectomy improves long-term outcomes in patients undergoing liver resection for cN0 iCCA. METHODS: We performed a retrospective cohort study on consecutive patients who underwent radical liver resection for cN0 iCCA at five tertiary referral centers. A propensity score based on preoperative data was calculated and used to generate stabilized inverse probability of treatment weight (IPTW). Overall and recurrence-free survival of patients undergoing adequate (≥6 retrieved lymph nodes) vs. inadequate lymphadenectomy were compared. Interactions between adequacy of lymphadenectomy and clinical variables of interest were explored through Cox IPTW regression. RESULTS: The study includes 706 patients who underwent curative surgery for cN0 iCCA. Four-hundred and seventeen (59.1%) received adequate lymphadenectomy. After a median follow-up of 33 months (IQR 18-77), median overall survival was 39 months (IQR 23-109) and median recurrence-free survival was 23 months (IQR 8-74). After stratification according to nodal status at final pathology, node-positive patients had longer overall survival (28 vs. 23 months; hazard ratio 1.82; 95% CI 1.14-2.90; p = 0.023) and disease-free survival (13 vs. 9 months; hazard ratio 1.35; 95% CI 1.14-1.59; p = 0.008) after adequate lymphadenectomy. Adequate lymphadenectomy significantly improved survival outcomes in patients without chronic liver disease, and in patients with less-advanced tumors (solitary tumors, tumor size <5 cm, carbohydrate antigen 19-9 <200 U/ml). CONCLUSIONS: Adequate lymphadenectomy provided better survival outcomes for patients with cN0 iCCA who were found to be node-positive at pathology, supporting the routine use of adequate lymphadenectomy for cN0 iCCA. IMPACT AND IMPLICATIONS: Lymphadenectomy is essential for the surgical staging of intrahepatic cholangiocarcinoma (iCCA). While its role in patients with preoperative suspicion of nodal metastases is implicit, the impact of lymphadenectomy on survival of patients with clinically node-negative (cN0) disease is still under debate. In this large retrospective study on patients who underwent surgical resection for cN0 iCCA, we show that adequate lymphadenectomy (i.e. retrieving ≥6 lymph nodes) significantly improves survival and lowers the risk of tumor recurrence. Lymphadenectomy during surgical resection of iCCA is actually underperformed by the surgical community, resulting in inadequate staging and possibly worse long-term outcomes. The results of this study should empower surgeons and clinicians to push for adequate lymphadenectomy even for cN0 iCCA. Since patients with no chronic liver disease and with less-advanced tumors receive a significant benefit from lymphadenectomy, our results might guide decision making in patients at high-risk of postoperative complications.

The Effect of a Liver Transplant Program on the Outcomes of Resectable Hepatocellular Carcinoma: A Nationwide Multicenter Analysis.

OBJECTIVE: To evaluate the effect of a liver transplantation (LT) program on the outcomes of resectable hepatocellular carcinoma (HCC). BACKGROUND: Surgical treatment of HCC includes both hepatic resection (HR) and LT. However, the presence of cirrhosis and the possibility of recurrence make the management of this disease complex and probably different according to the presence of a LT program. METHODS: Patients undergoing HR for HCC between January 2005 and December 2019 were identified from a national database of HCC. The main study outcomes were major surgical complications according to the Comprehensive Complication Index, posthepatectomy liver failure (PHLF), 90-day mortality, overall survival, and disease-free survival. Secondary outcomes were salvage liver transplantation (SLT) and postrecurrence survival. RESULTS: A total of 3202 patients were included from 25 hospitals over the study period. Three of 25 (12%) had an LT program. The presence of an LT program within a center was associated with a reduced probability of PHLF (odds ratio=0.38) but not with overall survival and disease-free survival. There was an increased probability of SLT when HR was performed in a transplant hospital (odds ratio=12.05). Among transplant-eligible patients, those who underwent LT had a significantly longer postrecurrence survival. CONCLUSIONS: This study showed that the presence of a LT program was associated with decreased PHLF rates and an increased probability to receive SLT in case of recurrence.

Defining Global Benchmarks for Laparoscopic Liver Resections: An International Multicenter Study.

OBJECTIVE: To establish global benchmark outcomes indicators after laparoscopic liver resections (L-LR). BACKGROUND: There is limited published data to date on the best achievable outcomes after L-LR. METHODS: This is a post hoc analysis of a multicenter database of 11,983 patients undergoing L-LR in 45 international centers in 4 continents between 2015 and 2020. Three specific procedures: left lateral sectionectomy (LLS), left hepatectomy (LH), and right hepatectomy (RH) were selected to represent the 3 difficulty levels of L-LR. Fifteen outcome indicators were selected to establish benchmark cutoffs. RESULTS: There were 3519 L-LR (LLS, LH, RH) of which 1258 L-LR (40.6%) cases performed in 34 benchmark expert centers qualified as low-risk benchmark cases. These included 659 LLS (52.4%), 306 LH (24.3%), and 293 RH (23.3%). The benchmark outcomes established for operation time, open conversion rate, blood loss ≥500 mL, blood transfusion rate, postoperative morbidity, major morbidity, and 90-day mortality after LLS, LH, and RH were 209.5, 302, and 426 minutes; 2.1%, 13.4%, and 13.0%; 3.2%, 20%, and 47.1%; 0%, 7.1%, and 10.5%; 11.1%, 20%, and 50%; 0%, 7.1%, and 20%; and 0%, 0%, and 0%, respectively. CONCLUSIONS: This study established the first global benchmark outcomes for L-LR in a large-scale international patient cohort. It provides an up-to-date reference regarding the "best achievable" results for L-LR for which centers adopting L-LR can use as a comparison to enable an objective assessment of performance gaps and learning curves.

An International Expert Delphi Consensus on Defining Textbook Outcome in Liver Surgery (TOLS).

OBJECTIVE: To reach global expert consensus on the definition of TOLS in minimally invasive and open liver resection among renowned international expert liver surgeons using a modified Delphi method. BACKGROUND: Textbook outcome is a novel composite measure combining the most desirable postoperative outcomes into one single measure and representing the ideal postoperative course. Despite a recently developed international definition of Textbook Outcome in Liver Surgery (TOLS), a standardized and expert consensus-based definition is lacking. METHODS: This international, consensus-based, qualitative study used a Delphi process to achieve consensus on the definition of TOLS. The survey comprised 6 surgical domains with a total of 26 questions on individual surgical outcome variables. The process included 4 rounds of online questionnaires. Consensus was achieved when a threshold of at least 80% agreement was reached. The results from the Delphi rounds were used to establish an international definition of TOLS. RESULTS: In total, 44 expert liver surgeons from 22 countries and all 3 major international hepato-pancreato-biliary associations completed round 1. Forty-two (96%), 41 (98%), and 41 (98%) of the experts participated in round 2, 3, and 4, respectively. The TOLS definition derived from the consensus process included the absence of intraoperative grade ≥2 incidents, postoperative bile leakage grade B/C, postoperative liver failure grade B/C, 90-day major postoperative complications, 90-day readmission due to surgery-related major complications, 90-day/in-hospital mortality, and the presence of R0 resection margin. CONCLUSIONS: This is the first study providing an international expert consensus-based definition of TOLS for minimally invasive and open liver resections by the use of a formal Delphi consensus approach. TOLS may be useful in assessing patient-level hospital performance and carrying out international comparisons between centers with different clinical practices to further improve patient outcomes.

Propensity-score Matched and Coarsened-exact Matched Analysis Comparing Robotic and Laparoscopic Major Hepatectomies: An International Multicenter Study of 4822 Cases.

OBJECTIVE: To compare the outcomes between robotic major hepatectomy (R-MH) and laparoscopic major hepatectomy (L-MH). BACKGROUND: Robotic techniques may overcome the limitations of laparoscopic liver resection. However, it is unknown whether R-MH is superior to L-MH. METHODS: This is a post hoc analysis of a multicenter database of patients undergoing R-MH or L-MH at 59 international centers from 2008 to 2021. Data on patient demographics, center experience volume, perioperative outcomes, and tumor characteristics were collected and analyzed. Both 1:1 propensity-score matched (PSM) and coarsened-exact matched (CEM) analyses were performed to minimize selection bias between both groups. RESULTS: A total of 4822 cases met the study criteria, of which 892 underwent R-MH and 3930 underwent L-MH. Both 1:1 PSM (841 R-MH vs. 841 L-MH) and CEM (237 R-MH vs. 356 L-MH) were performed. R-MH was associated with significantly less blood loss {PSM:200.0 [interquartile range (IQR):100.0, 450.0] vs 300.0 (IQR:150.0, 500.0) mL; P = 0.012; CEM:170.0 (IQR: 90.0, 400.0) vs 200.0 (IQR:100.0, 400.0) mL; P = 0.006}, lower rates of Pringle maneuver application (PSM: 47.1% vs 63.0%; P < 0.001; CEM: 54.0% vs 65.0%; P = 0.007) and open conversion (PSM: 5.1% vs 11.9%; P < 0.001; CEM: 5.5% vs 10.4%, P = 0.04) compared with L-MH. On subset analysis of 1273 patients with cirrhosis, R-MH was associated with a lower postoperative morbidity rate (PSM: 19.5% vs 29.9%; P = 0.02; CEM 10.4% vs 25.5%; P = 0.02) and shorter postoperative stay [PSM: 6.9 (IQR: 5.0, 9.0) days vs 8.0 (IQR: 6.0 11.3) days; P < 0.001; CEM 7.0 (IQR: 5.0, 9.0) days vs 7.0 (IQR: 6.0, 10.0) days; P = 0.047]. CONCLUSIONS: This international multicenter study demonstrated that R-MH was comparable to L-MH in safety and was associated with reduced blood loss, lower rates of Pringle maneuver application, and conversion to open surgery.

Benchmarks and Geographic Differences in Gallbladder Cancer Surgery: An International Multicenter Study.

BACKGROUND: High-quality surgery plays a central role in the delivery of excellent oncologic care. Benchmark values indicate the best achievable results. We aimed to define benchmark values for gallbladder cancer (GBC) surgery across an international population. PATIENTS AND METHODS: This study included consecutive patients with GBC who underwent curative-intent surgery during 2000-2021 at 13 centers, across seven countries and four continents. Patients operated on at high-volume centers without the need for vascular and/or bile duct reconstruction and without significant comorbidities were chosen as the benchmark group. RESULTS: Of 906 patients who underwent curative-intent GBC surgery during the study period, 245 (27%) were included in the benchmark group. These were predominantly women (n = 174, 71%) and had a median age of 64 years (interquartile range 57-70 years). In the benchmark group, 50 patients (20%) experienced complications within 90 days after surgery, with 20 patients (8%) developing major complications (Clavien-Dindo grade ≥ IIIa). Median length of postoperative hospital stay was 6 days (interquartile range 4-8 days). Benchmark values included ≥ 4 lymph nodes retrieved, estimated intraoperative blood loss ≤ 350 mL, perioperative blood transfusion rate ≤ 13%, operative time ≤ 332 min, length of hospital stay ≤ 8 days, R1 margin rate ≤ 7%, complication rate ≤ 22%, and rate of grade ≥ IIIa complications ≤ 11%. CONCLUSIONS: Surgery for GBC remains associated with significant morbidity. The availability of benchmark values may facilitate comparisons in future analyses among GBC patients, GBC surgical approaches, and centers performing GBC surgery.

Impact of Tumor Size on the Difficulty of Laparoscopic Major Hepatectomies: An International Multicenter Study.

INTRODUCTION: Although tumor size (TS) is known to affect surgical outcomes in laparoscopic liver resection (LLR), its impact on laparoscopic major hepatectomy (L-MH) is not well studied. The objectives of this study were to investigate the impact of TS on the perioperative outcomes of L-MH and to elucidate the optimal TS cutoff for stratifying the difficulty of L-MH. METHODS: This was a post-hoc analysis of 3008 patients who underwent L-MH at 48 international centers. A total 1396 patients met study criteria and were included. The impact of TS cutoffs was investigated by stratifying TS at each 10-mm interval. The optimal cutoffs were determined taking into consideration the number of endpoints which showed a statistically significant split around the cut-points of interest and the magnitude of relative risk after correction for multiple risk factors. RESULTS: We identified 2 optimal TS cutoffs, 50 mm and 100 mm, which segregated L-MH into 3 groups. An increasing TS across these 3 groups (≤ 50 mm, 51-100 mm, > 100 mm), was significantly associated with a higher open conversion rate (11.2%, 14.7%, 23.0%, P < 0.001), longer operating time (median, 340 min, 346 min, 365 min, P = 0.025), increased blood loss (median, 300 ml,  ml, 400 ml, P = 0.002) and higher rate of intraoperative blood transfusion (13.1%, 15.9%, 27.6%, P < 0.001). Postoperative outcomes such as overall morbidity, major morbidity, and length of stay were comparable across the three groups. CONCLUSION: Increasing TS was associated with poorer intraoperative but not postoperative outcomes after L-MH. We determined 2 TS cutoffs (50 mm and 10 mm) which could optimally stratify the surgical difficulty of L-MH.

Unexpected finding of a rare pathogenic germline BRCA1 variant in an intrahepatic cholangiocarcinoma using the Oncomine Focus DNA assay: clinical and diagnostic implications.

BACKGROUND: Cholangiocarcinoma (CCA) is a malignant tumor arising from the epithelial cells of the bile ducts and is the second most common liver cancer after hepatocellular carcinoma. Recently, our Institution launched a Comprehensive Genomic Profiling (CGP) program (named FPG500 program), set up to provide a complete molecular characterization through the TruSight Oncology 500 High Throughput (TSO500HT) solution and samples that do not reach pre-set sample quantity and/or quality thresholds required for TSO500HT, are addressed to Oncomine Focus DNA Assay (OFA) and the Archer's FusionPlex Lung Panel (AFL). METHODS AND RESULTS: Here we report the case of a patient with iCCA enrolled in the FPG500 program and screened by the orthogonal workflow (OFA/AFL). Although BRCA1 is not among the genes declared in the OFA panel, we unexpectedly detected a pathogenic variant in this gene (c.5278-2del, rs878853285). CONCLUSIONS: This case highlights the diagnostic capabilities of CGP, now widely used in both clinical practice and academic setting. The incidental involvement of BRCA1 focuses attention on the role of BRCA genes in biliary tract cancers. Finally, as an orthogonal test confirmed the germline origin of BRCA1 c.5278-2del variant, the germline implications of CGP need to be considered.

Bile duct injury following cholecystectomy: delayed referral to a tertiary care center is strongly associated with malpractice litigation.

BACKGROUND: Bile duct injury (BDI) following cholecystectomy is associated with malpractice litigation. Aim of this study was to evaluate risk factors for litigation in patients with BDI referred in a tertiary care center. METHODS: Patients treated for BDI between 1994 and 2016. Stabilized inverse probability therapy weighting was used and multivariable logistic regression analysis identified risk factors for malpractice litigation. RESULTS: Of the 211 treated patients, 98 met the inclusion criteria: early-referral group (<20 days; 51.0%), late-referral (≥20 days; 49.0%). 36 patients (36.7%) initiated malpractice litigation with verdict in favor of plaintiff in 86.7% of cases (median payment = €90 500, up to €600 000). Attempts at surgical and endoscopic repair before referral were significantly higher in late-referral group. Failed postoperative management (delayed referral, attempts at repair before referral) was one of the strongest predictors for litigation. Risk of litigation progressively increased from 23.8%, when referral time was within 19 days, to 54.5% (61-120 days), to 60.0% (121-210 days) and to 65.1% (211-365 days). DISCUSSION: Litigation rate after BDI was 37%. Delayed referral to tertiary care center was one of the strongest predictors for litigation. Prompt referral to tertiary experienced centers without any attempt at repair may reduce the risk of litigation.

Short and long-term outcomes after minimally invasive liver resection for single small hepatocellular carcinoma: An analysis of 714 patients from the IGoMILS (Italian group of minimally invasive liver surgery) registry.

BACKGROUND: Widespread use of minimally invasive liver surgery (MILS) contributed to the reduction of surgical risk of liver resection for hepatocellular carcinoma (HCC). Aim of this study was to analyze outcomes of MILS for single ≤3 cm HCC. METHODS: Patients who underwent MILS for single ≤3 cm HCC (November 2014 - December 2019) were identified from the Italian Group of Minimally Invasive Liver Surgery (IGoMILS) Registry. RESULTS: Of 714 patients included, 641 (93.0%) were Child-Pugh A; 65.7% were limited resections and 2.2% major resections, with a conversion rate of 5.2%. Ninety-day mortality rate was 0.3%. Overall morbidity rate was 22.4% (3.8% major complications). Mean postoperative stay was 5 days. Robotic resection showed longer operative time (p = 0.004) and a higher overall morbidity rate (p < 0.001), with similar major complications (p = 0.431). Child-Pugh B patients showed worse mortality (p = 0.017) and overall morbidity (p = 0.021), and longer postoperative stay (p = 0.005). Five-year overall survival was 79.5%; cirrhosis, satellite micronodules, and microvascular invasion were independently associated with survival. CONCLUSIONS: MILS for ≤3 cm HCC was associated with low morbidity and mortality rates, showing high safety, and supporting the increasing indications for surgical resection in these patients.

Results from the european survey on preoperative management and optimization protocols for PeriHilar cholangiocarcinoma.

BACKGROUND: Major surgery, along with preoperative cholestasis-related complications, are responsible for the increased risk of morbidity and mortality in perihilar cholangiocarcinoma (pCCA). The aim of the present survey is to provide a snapshot of current preoperative management and optimization strategies in Europe. METHODS: 61 European centers, experienced in hepato-biliary surgery completed a 59-questions survey regarding pCCA preoperative management. Centers were stratified according to surgical caseload (<5 and ≥ 5 cases/year) and preoperative management protocols' application. RESULTS: The overall case volume consisted of 6333 patients. Multidisciplinary discussion was routinely performed in 91.8% of centers. Most respondents (96.7%) recognized the importance of a well-structured preoperative protocol. The preferred method for biliary drainage was percutaneous transhepatic biliary drainage (60.7%) while portal vein embolization was the preferred technique for liver hypertrophy (90.2%). Differences in preoperative pathologic confirmation of malignancy (35.8% vs 28.7%; p < 0.001), number of mismanaged referred patients (88.2% vs 50.8%; p < 0.001), biliary drainage (65.1% vs 55.6%; p = 0.015) and liver function evaluation (37.2% vs 5.6%; p = 0.001) were found between centers according to groups' stratification. CONCLUSION: The importance of a correct preoperative management is recognized. Nevertheless, the current lack of guidelines leads to wide heterogeneity of behaviors among centers. This survey can provide recommendations to improve pCCA perioperative outcomes.

Hepatectomy Versus Sorafenib in Advanced Nonmetastatic Hepatocellular Carcinoma: A Real-life Multicentric Weighted Comparison.

OBJECTIVE: The aim of the study was to compare SURG vs SOR regarding the OS and progression-free survival (PFS) in a real-world clinical scenario. BACKGROUND DATA: The treatment for advanced nonmetastatic HCC belonging to the Barcelona Clinic Liver Cancer stage C (BCLC C) is still controversial. METHODS: BCLC C patients without extrahepatic spread and tumoral invasion of the main portal trunk were considered. Surgical patients were obtained from the HE.RC.O.LE.S. Register, whereas sorafenib patients were obtained from the ITA.LI.CA register The inverse probability weighting (IPW) method was adopted to balance the confounders between the 2 groups. RESULTS: Between 2008 and 2019, 478 patients were enrolled: 303 in SURG and 175 in SOR group. Eastern Cooperative Oncological Group Performance Status (ECOG-PS), presence of cirrhosis, steatosis, Child-Pugh grade, hepatitis B virus and hepatitis C virus, alcohol intake, collateral veins, bilobar disease, localization of the tumor thrombus, number of nodules, alpha-fetoprotein, age, and Charlson Comorbidity index were weighted by IPW to create two balanced pseudo-populations: SURG = 374 and SOR = 263. After IPW, 1-3-5 years OS was 83.6%, 68.1%, 55.9% for SURG, and 42.3%, 17.8%, 12.8% for SOR (P < 0.001). Similar trends were observed after subgrouping patients by ECOG-PS = 0 and ECOG-PS >0, and by the intrahepatic location of portal vein invasion. At Cox regression, sorafenib treatment (hazard ratio 4.436; 95% confidence interval 3.19-6.15; P < 0.001) and Charlson Index (hazard ratio 1.162; 95% confidence interval 1.06-1.27; P = 0.010) were the only independent predictors of mortality. PFS at 1-3-5 years were 65.9%, 40.3%, 24.3% for SURG and 21.6%, 3.5%, 2.9% for SOR (P = 0.007). CONCLUSIONS: In BCLC C patients without extrahepatic spread but with intrahepatic portal invasion, liver resection, if feasible, was followed by better OS and PFS compared with sorafenib.